The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review.

Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies. We have also analyzed the cellular biology and the interactions between GBM and the surrounding environment.

Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation.

OBJECTIVES: Bilateral chronic high frequency stimulation of the subthalamic nucleus (STN), through the stereotactical placement of stimulating electrodes, effectively improves the motor symptoms of severe Parkinson's disease. Intraoperative neurophysiological and clinical monitoring techniques (neuronal electrical activity recording and intraoperative stimulation) may improve and refine the localisation of the nucleus. The objective of this work was to compare the preoperative CT and MRI localisation with the intraoperative neurophysiological identification of STN. The relation between the localisation of the STN and the position of the most effective contact of the permanent quadripolar electrode at a 3 month and 1 year follow up was also studied. METHODS: Fourteen consecutive parkinsonian patients were submitted to bilateral implant for STN stimulation. All the patients underwent a standard MRI and stereotactic CT to obtain, by image fusion and localisation software, the stereotactical coordinates of STN. The STN extension and boundaries were identified by a semimicrorecording of the neuronal electrical activity. The definitive quadripolar electrode was positioned to locate at least two contacts within the STN recording area. Intraoperative macrostimulation was performed to confirm the correct position of the electrode. Postoperative clinical evaluation of the effects of stimulation was checked for each contact of the quadripolar electrode testing the improvement on contralateral rigidity to select the best contact. This evaluation was repeated at 3 months and 1 year after surgery. RESULTS: In 35.7% of the procedures it was necessary to perform more than one track to get a recording of neuronal activity consistent with STN. The mean position of the central point of all the 28 STN recording areas in respect of the AC-PC line midpoint was 2.7 mm posterior (SD 0.7), 3.8 mm inferior (SD 1.1), and 11.6 mm lateral (SD 0.9), and the mean distance between the anatomical target and the central point of the STN as defined by intraoperative recording was 0.5 mm (SD 0.5) on the anteroposterior plane, 0.7 mm (SD 0.7) on the lateral plane, and 0.9 mm (SD 0.6) on the vertical plane. At 1 year the mean position of the central point of the most effective contact of the electrode in respect of the AC-PC line midpoint was 1.7 mm posterior (SD 0.9), 1.7 mm inferior (SD 1.5), and 12.3 mm lateral (SD 0.9). CONCLUSION: The results highlight the role of the intraoperative recording to get a more accurate localisation of the STN in surgery for Parkinson's disease, allowing the identification of the boundaries and of the extension of the nucleus. The most effective contact of the quadripolar electrode was always in the upper part of the STN recording area or immediately above it, suggesting a role of this region in the clinical effectiveness of the STN electrical stimulation.

High-frequency electrical stimulation of the subthalamic nucleus in Parkinson's disease: kinetic and kinematic gait analysis.

In the advanced phase of Parkinson's disease (PD), gait disturbances represent one of the main causes of disability. Several studies demonstrated that high-frequency electrical stimulation (HFS) of the subthalamic nucleus (STN) significantly improves the motor symptoms of PD. This study was finalised to quantitatively analyze the effect of STN HFS on gait of PD patients, through a three-dimensional gait analysis system. Ten PD patients were studied, with and without STN HFS. The results demonstrated that STN HFS significantly improves all the main gait parameters in PD patients.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters.

OBJECTIVE: To investigate the relation between the variation of the parameters of stimulation and the clinical effectiveness in parkinsonian patients treated with deep brain stimulation of the subthalamic nucleus (STN), to provide information on the electrical parameter setting and the mechanism of action of deep brain stimulation. METHODS: Ten patients with Parkinson's disease bilaterally implanted in the STN were studied. For every patient the intensity of the stimulus necessary to obtain the disappearance of contralateral wrist rigidity (required clinical effect, RCE) and the side effect threshold in 20 different conditions of stimulation, coupling four pulse width values (60, 120, 210, 450 micros) with five rate values (10, 50, 90, 130, 170 Hz) were determined. All the patients were tested after a 12 hour withdrawal of antiparkinsonian drugs, and the clinical evaluation was double blind. RESULTS: In all the patients it was impossible to obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate values, the intensity-pulse width curves (IPWCs) for the RCE and for the side effect threshold showed a hyperbolic trend. For every pulse width value, increasing the rate from 90 to 130 and to 170 Hz progressively decreased the intensity of the stimulus necessary to reach the RCE, but the differences were not significant. Within the same rate value, the progressive reduction of the stimulus intensity necessary to obtain the RCE, obtained with the lengthening of the pulse width was significant (p<0.05) only comparing 60 with 210 micros and 60 with 450 micros. CONCLUSIONS: The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation.

Acute brain swelling during removal of supratentorial cystic lesion caused by contralateral extradural hematoma: case report.

BACKGROUND: Protrusion of the cortex through a bone flap in the course of surgery is a very serious event and, if it persists, the procedure must be suspended, the cause sought, and the problem resolved. CASE DESCRIPTION: We report the case of a 13-year-old boy whose brain underwent sudden swelling during removal of a supratentorial cystic lesion. The operation was suspended at once and an emergency CT scan was performed. It revealed a large contralateral extradural hematoma, which was removed immediately. CONCLUSIONS: We considered the following possible mechanisms of the emergency: bleeding of bone at the site of the supposed piercing by the headrest pin and/or a vacuum mechanism consequent upon removal of the large cystic lesion. Our aims are to emphasize the importance of gauging the thickness of a child's skull before fixing the head in the headrest, especially when chronic intracranial hypertension is present, and the need to suspend the operation for CT scanning in the event of uncontrollable brain swelling.

Variations in regional cerebral blood flow investigated by single photon emission computed tomography with technetium-99m-d, l-hexamethylpropyleneamineoxime = l-h during temporary clipping in intracranial aneurysm surgery: preliminary results.

Single photon emission computed tomography with technetium-99m-d, l-hexamethylpropyleneamineoxime was used to assess variations in regional cerebral blood flow during temporary clipping in the course of intracranial aneurysm surgery and during the postoperative period in 20 patients, 14 of whom underwent temporary clipping. Of these 14 patients (Group A), 9 had aneurysms of the anterior communicating artery, 2 had aneurysms of the middle cerebral artery, and 3 had aneurysms of the carotid siphon. Temporary clips were applied, according to the site of the lesion, on A1, on the trunk of the middle cerebral artery, or on the trunk of the internal carotid artery. The occlusion time ranged from 2 to 31 minutes. The six patients who did not undergo temporary clipping served as controls (Group B), as follows: three had aneurysms of the posterior communicating artery, one of the anterior communicating artery, one of the middle cerebral artery, and one of the internal carotid artery. All patients were investigated with cerebral single photon emission computed tomography preoperatively, perioperatively, and postoperatively. In all the patients of Group A, the preliminary results of the study show a sharp fall in the perfusion of the territories of the temporarily clipped parent vessel and practically a complete recovery within 2 to 7 days of surgery, with no significant neurological symptoms. No similar disturbance of perfusion was found in the patients of Group B.

Clinical and neuroradiological correlations in a patient with a wandering retained air gun pellet in the brain.

The authors present the case of a patient with an air gun pellet that moved from the ventricular system into the subarachnoid space of C2-C3, from where it was successfully removed by interlaminotomy.

Neuralgia of the intermediate nerve combined with trigeminal neuralgia: case report.

An unusual case of a combination of trigeminal and intermediate nerve neuralgia is presented, caused by vascular compression of both of the nerve roots by different vessels. Because the neuralgia of the intermediate nerve could be cured by a vascular decompression operation, it is suggested to include it among the hyperactive dysfunction syndromes of cranial nerves caused by vascular compression at the root entry zone of the nerves. Therefore also for treatment of this neuralgia the non-destructive vascular decompression operation should be taken into consideration.

Serial stereotactic biopsy of brain stem expanding lesions. Considerations on 45 consecutive cases.

Fourty-five patients affected by brain stem expanding lesions underwent serial stereotactic biopsy between 1978 and 1986. The definitive histological diagnosis allowed the definitive treatment of extrinsic tumours and non-neoplastic lesions. In patients affected from glial tumours the serial stereotactic biopsy allowed the histological grading and the definition of the growth modalities at the superior boundaries of the tumours. These data have been utilized to guide the choice of treatment. The future perspectives of stereotactic biopsies are discussed in view of the therapeutic results obtained in this series and in other series reported in the literature.

Surgical approach to giant aneurysms of the anterior circulation.

The surgical approach to cerebral giant aneurysms is still a source of great concern. We describe our experience with giant aneurysms of the anterior circulation and discuss the different surgical techniques adopted. During the period January 1972-December 1985, a total of 33 patients were operated upon at the Istituto Neurologico "C. Besta" of Milan for a giant aneurysm of the anterior circulation. Nineteen cases had suffered subarachnoid haemorrhage before admission; in 14 cases the hospitalization was due to evidence of mass effect on the surrounding neurovascular structures. All aneurysms were directly approached: in 24 cases the neck was occluded by a suitable clip, in 4 cases intramural thrombosis was attempted, in 3 cases the aneurysms were definitively trapped and in one case aneurysmorrhaphy was performed after resection of the sac. Operative mortality was 12%. Long-term follow-up shows good results whenever exclusion of the aneurysm from cerebral circulation had been achieved, either after removal of the sac or not; on the contrary, only fair or poor results were evident when other surgical techniques were adopted, either electively or out of necessity. The importance of intraoperative protection and monitoring of brain function is stressed.

Cell kinetics of gliomas by serial stereotactic biopsy.

The potential proliferative activity of glial tumors has been investigate by serial stereotactic biopsies and by "in vitro" 3H-thymidine incorporation procedure (labeling index, LI). The methodology of this combined approach and the preliminary results in 33 patients are reported. Cell kinetic data have been matched with the histological classification (W.H.O.).

Cell kinetics of neuroepithelial tumors in serial stereotactic biopsies. A new combined approach.

33 consecutive patients with brain glial tumors underwent serial stereotactic biopsies and (3H)-thymidine in vitro investigation. The labeling index has been determined in each case and matched with the WHO histological classification. The feasibility and the accuracy of cell kinetics study applied to stereotactic biopsies are discussed in view of future application for prognostic purposes. Particular attention is given to the description of the method.